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NCT02655419

Determine the PK and Safety and Tolerability of ATM-AVI for the Treatment of cIAIs in Hospitalized Adults (REJUVENATE)

Completed Phase 2 Results posted Last updated 2 April 2020
What this trial tests

Phase 2 trial testing ATM-AVI in Complicated Intra-Abdominal Infections, cIAIs in 40 participants. Completed in 26 October 2017.

Timeline
19 May 2016
Primary endpoint
26 October 2017
26 October 2017

Quick facts

Lead sponsorPfizer
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment40
Start date19 May 2016
Primary completion26 October 2017
Estimated completion26 October 2017
Sites11 locations across France, Germany, Spain

Drugs / interventions tested

Conditions studied

Sponsor

Pfizer — full company profile →

Who can join

Adults 18 to 90, any sex, with Complicated Intra-Abdominal Infections, cIAIs. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Plasma Concentration of Aztreonam (ATM): Sparse Sampling at Day 1, 0 hr Primary · Predose (0 hr) on Day 1

All participants were to have sparse pharmacokinetics (PK) sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above lower limit of quantification (LLOQ). LLOQ for ATM was 0.1 microgram per milliliter (mcg/ml).

GroupValue95% CI
ATM-AVI+ Metronidazole:Low AVI Dose Cohort0.1± NA
Plasma Concentration of Aztreonam (ATM): Sparse Sampling at Day 1, 0.42 hr Primary · 0.42 hr Post dose on Day 1

All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.

GroupValue95% CI
ATM-AVI+ Metronidazole:Low AVI Dose Cohort39.0± 262.0
ATM-AVI + Metronidazole: High AVI Dose Cohort39.4± 58.1
Plasma Concentrations of Aztreonam (ATM): Sparse Sampling at Day 1, 3.25 hr Primary · 3.25 hr Post dose on Day 1

All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.

GroupValue95% CI
ATM-AVI+ Metronidazole:Low AVI Dose Cohort55.7± 16.0
ATM-AVI + Metronidazole: High AVI Dose Cohort58.5± 36.3
Plasma Concentrations of Aztreonam (ATM): Sparse Sampling at Day 1, 5 hr Primary · 5 hr Post dose on Day 1

All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.

GroupValue95% CI
ATM-AVI + Metronidazole: Low AVI Dose Cohort28.8± 23.9
ATM-AVI + Metronidazole: High AVI Dose Cohort31.5± 50.8
Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 1, 0 hr Primary · Predose (0 hr) on Day 1

All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 nanogram per milliliter (ng/ml).

GroupValue95% CI
ATM-AVI + Metronidazole: Low AVI Dose Cohort24.9± NA
Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 1, 0.42 hr Primary · 0.42 hr Post dose on Day 1

All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.

GroupValue95% CI
ATM-AVI + Metronidazole: Low AVI Dose Cohort7852.6± 279.2
ATM-AVI + Metronidazole: High AVI Dose Cohort9801.5± 61.8
Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 1, 3.25 hr Primary · 3.25 hr Post dose on Day 1

All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.

GroupValue95% CI
ATM-AVI + Metronidazole: Low AVI Dose Cohort9976.5± 25.8
ATM-AVI + Metronidazole: High AVI Dose Cohort12982.7± 49.7
Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 1, 5 hr Primary · 5 hr Post dose on Day 1

All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.

GroupValue95% CI
ATM-AVI + Metronidazole: Low AVI Dose Cohort4086.6± 35.3
ATM-AVI + Metronidazole: High AVI Dose Cohort5549.0± 76.6
Plasma Concentration of Aztreonam (ATM): Sparse Sampling at Day 4, 0 hr Primary · Predose (0 hr) on Day 4

All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.

GroupValue95% CI
ATM-AVI + Metronidazole: High AVI Dose Cohort19.7± 29.0
Plasma Concentration of Aztreonam (ATM): Sparse Sampling at Day 4, 2.75 hr Primary · 2.75 hr Post dose on Day 4

All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.

GroupValue95% CI
ATM-AVI + Metronidazole: High AVI Dose Cohort46.4± 19.5
Plasma Concentration of Aztreonam (ATM): Sparse Sampling at Day 4, 5 hr Primary · 5 hr Post dose on Day 4

All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for ATM was 0.1 mcg/ml.

GroupValue95% CI
ATM-AVI + Metronidazole: High AVI Dose Cohort16.5± 37.3
Plasma Concentration of Avibactam (AVI): Sparse Sampling at Day 4, 0 hr Primary · Predose (0 hr) on Day 4

All participants were to have sparse PK sampling on Day 1; the first sequentially enrolled 25 participants in study were to have intensive PK sampling on Day 4 while the remaining participants were to have sparse sampling on Day 4. Data was summarized only for observations above LLOQ. LLOQ for AVI was 10 ng/ml.

GroupValue95% CI
ATM-AVI + Metronidazole: High AVI Dose Cohort4048.8± 24.3

Adverse events — posted to ClinicalTrials.gov

Time frame: From first dose of study drug up to the LFU visit (up to maximum of 38 days). Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

ATM-AVI+ Metronidazole: Low AVI Dose Cohort
Serious: 4/16 (25%)
Deaths: 0/16
ATM-AVI + Metronidazole: High AVI Dose Cohort
Serious: 5/18 (28%)
Deaths: 1/18

Serious adverse events (12 terms)

ReactionSystemATM-AVI+ Metronidazole: Lo…ATM-AVI + Metronidazole: H…
Intestinal ischaemiaGastrointestinal disorders
Intra-abdominal haematomaGastrointestinal disorders
Pancreatitis acuteGastrointestinal disorders
Abdominal wall infectionInfections and infestations
SepsisInfections and infestations
Arterial injuryInjury, poisoning and procedural complications
Postoperative ileusInjury, poisoning and procedural complications
Colon cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute kidney injuryRenal and urinary disorders
Acute respiratory distress syndromeRespiratory, thoracic and mediastinal disorders
Respiratory distressRespiratory, thoracic and mediastinal disorders
Haemorrhage subcutaneousSkin and subcutaneous tissue disorders
Other adverse events (26 terms — click to expand)

ReactionSystemATM-AVI+ Metronidazole: Lo…ATM-AVI + Metronidazole: H…
Hepatic enzyme increasedInvestigations
DiarrhoeaGastrointestinal disorders
AnaemiaBlood and lymphatic system disorders
Abdominal pain lowerGastrointestinal disorders
NauseaGastrointestinal disorders
OedemaGeneral disorders
ThrombocytosisBlood and lymphatic system disorders
Cardiac failure congestiveCardiac disorders
Vision blurredEye disorders
Paraesthesia oralGastrointestinal disorders
Generalised oedemaGeneral disorders
Drug-induced liver injuryHepatobiliary disorders
HypertransaminasaemiaHepatobiliary disorders
Chronic hepatitis CInfections and infestations
PneumoniaInfections and infestations
Tooth abscessInfections and infestations
Limb injuryInjury, poisoning and procedural complications
HyperuricaemiaMetabolism and nutrition disorders
Back painMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders
Confusional statePsychiatric disorders
Hallucination, visualPsychiatric disorders
Dermatitis atopicSkin and subcutaneous tissue disorders
RashSkin and subcutaneous tissue disorders
Skin exfoliationSkin and subcutaneous tissue disorders
Testicular swellingReproductive system and breast disorders

Most-reported serious reactions: Intestinal ischaemia, Intra-abdominal haematoma, Pancreatitis acute, Abdominal wall infection, Sepsis, Arterial injury, Postoperative ileus, Colon cancer.

Data from ClinicalTrials.gov NCT02655419 adverse events section.

Sponsor's own description

Determine the PK and safety and tolerability of aztreonam-avibactam (ATM-AVI) in the treatment of hospitalized adults with cIAI

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. New β-Lactamase Inhibitors in the Clinic.
    Papp-Wallace KM, Bonomo RA. · · 2016 · cited 121× · PMID 27208767 · DOI 10.1016/j.idc.2016.02.007
  2. Pharmacokinetics and safety of aztreonam/avibactam for the treatment of complicated intra-abdominal infections in hospitalized adults: results from the REJUVENATE study.
    Cornely OA, Cisneros JM, Torre-Cisneros J, Rodríguez-Hernández MJ, et al · · 2020 · cited 98× · PMID 31828337 · DOI 10.1093/jac/dkz497
  3. New Carbapenemase Inhibitors: Clearing the Way for the β-Lactams.
    Vázquez-Ucha JC, Arca-Suárez J, Bou G, Beceiro A. · · 2020 · cited 87× · PMID 33291334 · DOI 10.3390/ijms21239308
  4. Avibactam Pharmacokinetic/Pharmacodynamic Targets.
    Nichols WW, Newell P, Critchley IA, Riccobene T, et al · · 2018 · cited 83× · PMID 29610208 · DOI 10.1128/aac.02446-17
  5. Defining the Role of Novel β-Lactam Agents That Target Carbapenem-Resistant Gram-Negative Organisms.
    Tamma PD, Hsu AJ. · · 2019 · cited 55× · PMID 30793757 · DOI 10.1093/jpids/piz002
  6. Dose selection for aztreonam-avibactam, including adjustments for renal impairment, for Phase IIa and Phase III evaluation.
    Das S, Riccobene T, Carrothers TJ, Wright JG, et al · · 2024 · cited 19× · PMID 38252170 · DOI 10.1007/s00228-023-03609-x
  7. Management of community-acquired bacterial pneumonia in adults: Limitations of current antibiotics and future therapies.
    Nayar S, Hasan A, Waghray P, Ramananthan S, et al · · 2019 · cited 6× · PMID 31670301 · DOI 10.4103/lungindia.lungindia_38_19
  8. Clinical efficacy, safety and pharmacokinetics of novel β-lactam/β-lactamase inhibitor combinations: a systematic review.
    Alarcia-Lacalle A, Canut-Blasco A, Solinís MÁ, Isla A, et al · · 2025 · cited 3× · PMID 40583996 · DOI 10.1093/jacamr/dlaf096

Verify or expand the search:

Other trials of ATM-AVI

Trials testing the same drug.

Other recruiting trials for Complicated Intra-Abdominal Infections, cIAIs

Currently open trials in the same condition.

Other Pfizer trials

Trials by the same sponsor.

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